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Mutant DLX 3 disrupts odontoblast polarization and dentin formation
1Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Developmental Biology
|June 1, 2010
Summary
Mutant DLX3 (MT-DLX3) causes Tricho-dento-osseous (TDO) syndrome by disrupting odontoblast differentiation and promoting apoptosis. This leads to reduced dentin, abnormal tubules, and taurodontism in transgenic mice.
Area of Science:
- Genetics and Developmental Biology
- Oral Biology
- Biochemistry
Background:
- Tricho-dento-osseous (TDO) syndrome is an autosomal dominant disorder affecting bone and teeth.
- A mutation in the Distal-Less 3 (DLX3) gene underlies most TDO cases.
- The in vivo role of mutant DLX3 (MT-DLX3) in dentin development requires further investigation.
Purpose of the Study:
- To investigate the in vivo effects of MT-DLX3 on dentin development using a transgenic mouse model.
- To elucidate the molecular mechanisms by which MT-DLX3 impacts odontoblast function and dentin formation.
Main Methods:
- Generation of transgenic (TG) mice expressing MT-DLX3 under the control of a mouse 2.3 Col1A1 promoter.
- Radiographic, microcomputed tomography, SEM, histological, and immunohistochemical analyses of TG mouse teeth.
- TUNEL assays and Western blotting to assess apoptosis and gene expression in odontoblasts.
Main Results:
- TG mice exhibited radiographic dentin defects and enlarged pulp, mirroring TDO clinical features.
- Reduced mineralized dentin, abnormal dentinal tubules, disrupted odontoblast polarization, and decreased odontoblast numbers were observed.
- Enhanced odontoblast apoptosis, increased caspase-3 expression, and reduced expression of Runx2, Wnt 10A, and TBC1D19 were noted in TG mice.
Conclusions:
- MT-DLX3 disrupts odontoblast cytodifferentiation, leading to apoptosis and impaired dentin matrix production and mineralization.
- Altered TBC1D19 expression contributes to odontoblast polarity disruption and apoptosis.
- The transgenic model provides insights into TDO pathogenesis and odontoblast biology.
